Several nucleic acid amplification techniques are already known, e.g. the Polymerase Chain Reaction (PCR). However many of these techniques (including PCR) suffer from the disadvantage that they specifically amplify a target sequence (amplicon) present within the sample of interest. This amplicon, once generated, can easily contaminate a laboratory working area in which strict controls are not maintained. Such contamination can render subsequent amplification reactions suspect, and can require a cessation of testing and the initiation of expensive decontamination procedures.
Techniques such as PCR, which detect the presence of a sequence by amplifying its number to detectable levels, are known as Target Amplification systems. In contrast, several techniques are known which amplify a signal to detectable levels, usually following the binding of a detector molecule to the molecule of interest, without amplification of said molecule. These are referred to as Signal Amplification techniques.
One such system Chiron Corporation (Urdeaet al., U.S. Pat. No. 5,681,697 and references cited therein) is known as the branched DNA system (bDNA). This system relies on the binding to the target molecule, of a large number of detector probes, which contain within their sequence a site for hybridisation of a non-target specific sequence. This sequence acts as the site for hybridisation of a pre-synthesized branched DNA structure with numerous sites for the hybridisation of secondary branches or of detection probes. One of the main disadvantages of this system is the large number of components required to generate the final structure to which the detection probes adhere. In addition, the many hybridisation steps involved in the assembly process render the system susceptible to the production of non-specific background signal.
Other target detection systems known in the art include U.S. Pat. No. 5,451,503, WO 98/02580. WO 97/42346 and U.S. Pat. No. 5,681,697.